Title of proposed idea: Regulatory Science Initiative  

Nominator: NIH Institutes/Centers

 Major obstacle/challenge to overcome: The rapid pace of scientific discovery coupled with development of new technologies presents a challenge to researchers, clinical investigators, and regulators as they work to translate basic scientific advances into approved medical products.  Basic and preclinical research has been performed in large part independent of regulatory issues. In addition, it is clear that novel technologies and approaches to medical research are outpacing the ability of our regulatory system to incorporate them into current review practices and guidelines. To overcome these obstacles, NIH should support strategic initiatives that are essential to the translation of NIH funded discoveries into diagnostic and therapeutics.

Emerging scientific opportunity ripe for Common Fund investment:   An investment in Regulatory Science will benefit all stakeholders by helping to advance and incorporate cutting-edge science into regulatory decision making and helping to develop improved tools, standards and approaches for assessing the safety, efficacy, quality and performance of medical products. Major advances in genomics and genomics-based medicine are also creating potential scenarios in the clinical setting that are relatively new to the FDA regulatory process. Moreover, the unprecedented partnership between the NIH and FDA through the Joint Leadership Council provides an extraordinary opportunity to coordinate therapy development efforts, including regulatory decision-making guidelines, between the two agencies. 

Common Fund investment that could accelerate scientific progress in this field: A number of scientific opportunities are ripe for investment in the area of Regulatory science and across the therapeutics development pipeline. For instance:

• Advances stemming from next generation sequencing technologies to help set the stage for personalized medicine, and other novel, genomics-based approaches to drug development, and treatments, such gene-editing, regulatory RNAs, gene –silencing or transcriptional activation
• Nanotechnology, microfluidics, and stem cell technologies to alter the way experimental agents are tested for safety and efficacy, and ultimately delivered to patients as therapies
• New approaches to predictive toxicology including high-throughput screening strategies/models, new in-silico approaches and computer-simulation models
• Development of bioinformatics tools and approaches for data mining and meta-analyses on safety and efficacy that capitalizes on the increasing volumes of clinical and medical product-related information in data repositories,
• Novel approaches of conducting clinical trials for rare and neglected diseases

Potential impact of Common Fund investment: Pre-clinical and clinical investigators, and other researchers who are engaged in the diagnostics and therapeutics development industries will benefit from having a more rapid integration of evidence-based knowledge into a regulatory framework, thereby quickening the pace at which basic science advances can move into the therapy development realm. For instance, in the area of stem-cell technologies, the NIH and FDA are working together to identify and define markers and characteristics of “stemness”, thus providing standards that the entire field can use for purposes of comparing studies and preparing for regulatory considerations.  The possibility of individualized, autologous utility of stem cell-derived therapeutics, organs, tissues, and other biomedical products are fast becoming a reality. Other emerging areas in regulatory science will advance, such as nanomedicine, personalized medicine, efficient and expeditious clinical trial designs, predictive toxicology, and biomimetic models that are able to simulate human conditions and better predict safety and efficacy.  The NIH-FDA joint efforts in these areas would help to pave a clearer and more transparent scientific and regulatory path for the scientific community that will impact therapeutics product development and clinical practice.

Title of proposed idea: Targeting the Dynamic Complexome

Nominator: Innovation Brainstorm participants

Major obstacle/challenge to overcome: The spatial and temporal dynamics of protein complexes and complex-drug interactions are difficult to characterize (and predict). In part, this contributes to the well known in vitro/in vivo discrepancy between predicted and actual drug action and efficacy. Primarily, this is due to current limitations of in vivo validation processes. Experimental mapping of the dynamic complexome in normal and disease states would add significantly to overcoming this obstacle. Much more rational design and screening methods are important for developing safe and effective drugs that specifically target complexes.

Emerging scientific opportunity ripe for Common Fund investment: Recent progress in the development of tools and methods to map dynamic protein-protein interactions provide a mechanism through which disease pathogenesis can be better understood and new drugs can be designed. Specific challenges must be overcome for these possibilities to become reality.

Common Fund investment that could accelerate scientific progress in this field: Common Fund (CF) investments in the following would have a transformative impact on the identification of new drugs, the functional annotation of existing drugs, and the identification and testing of candidates for polypharmacologic approaches:

Potential impact of Common Fund investment: Investment in this area would benefit basic and applied studies. Identification of new functionally distinct complexes that define cellular pathways will increase knowledge about pathways and signaling mechanisms shared among diseases and conditions. Mapping the complexome may have as much potential for distinguishing disease states as does mapping the genome. Progress in this area will also likely yield small molecules as probes for clinical samples and tissue engineering models. Clinically relevant impact also includes the identification of new drugs that are specific, effective, and which have better side-effect profiles than most currently used therapeutics.

Title of proposed idea: Group Effects

Nominator: Innovation Brainstorm participants

Major obstacle/challenge to overcome: Exposures are highly variable and dynamic throughout the lifetime of an individual. Needed are systematic, unbiased screens for studying how multiple factors (e.g. microbiological, chemical, lifestyle and dietary exposures) interact to contribute to susceptibility to disease, disease progression, and treatment outcomes. In addition to curating/annotating data obtained using current models, improved testing systems are needed that are equipped to analyze multi-factorial issues.

Emerging scientific opportunity ripe for Common Fund investment:  Several opportunities exist to address the need for better models and analytic tools. These include the availability of inexpensive exposure screening tools (e.g. virochip, protein adducts) and bioinformatic techniques that can handle large, clinical datasets to track exposures. The development of screening tools, methods, and model systems that are particularly well suited for studying mechanisms of environmental influence also provide opportunities in this area. Point-of-care tools are likely to be especially useful to monitor exposure in global and other low-resource settings. Expanding these toward multiplex capability is another opportunity.

Common Fund investment that could accelerate scientific progress in this field:  The Common Fund (CF) could shift the curve to accelerate progress by expanding the number and quality of tools to systematically measure multiple exposures and by supporting the development of computational tools that will support multifactorial research: viral, bacterial, chemical, and dietary. Data handling for these types of studies is an enormous challenge. A database that catalogs and characterizes model systems that are suitable for studying multifactorial research would also be helpful.

Potential impact of Common Fund investment: Implementing projects in this area could have significant impact in helping to better clarify the age-old question of the relative influences of “nature and nurture;” yet, it would go further by ultimately explaining how complex mixtures of genetic loci and environmental exposures influence health and disease susceptibility. In time, these insights will point to preventive strategies that help to fulfill the goals of personalized medicine.